Bachelor of Science (BS), Ohio University, 2022, Biological Sciences

Lung cancer is the second most prevalent cancer in both men and women in the United States, and it currently the leading cause of cancer-related deaths. While there are current standard treatments for lung cancer, these treatments are not effective enough, and can lead to drug resistance, severe side effects, and even recurrence of the cancer and death. It is easy to see that better anticancer therapies are urgently needed. It has been shown that many cancer types, including Non-Small Cell Lung Cancer (NSCLC), which makes up 84% of all lung cancer diagnosis, are addicted to glucose and are sensitive to glucose deprivation, ultimately resulting in cancer cell-death. DRB18 is a small molecule compound developed at Ohio University that has been shown to target and inhibit glucose transporters (GLUTs), which are responsible for the uptake of glucose into cells, particularly cancer cells. DRB18 has been shown to be effective in inhibiting cancer cell growth in vitro (cell culture) and in vivo (nude mice) without noticeable side effects. While this may be a promising anticancer therapy by itself, combining DRB18 with an FDA-approved anticancer drugs Paclitaxel, Trametinib, or Brigatinib maximized the efficacy of the treatment in vitro in NSCLC A549 cells, and combination treatment of DRB18 + Paclitaxel resulted in shrunken A549 xenograft tumors in vivo, without increasing unwanted side effects. This combination therapy has the potential to benefit cancer patients for decades to come.

Master of Science, The Ohio State University, 2009, Allied Medicine

The prevalence of overweight and obesity and other nutritionally related disease development among pediatric cancer survivors is well known to be above national norms. This is a retrospective cohort study designed to investigate the relationship between childhood cancer survivorship and nutritionally related disease development. The objective of this study was to gather data from existing pediatric cancer survivors in order to study disease development in relation to the type of cancer the patient had, the course of treatment, and to nutrition care that patient may have received. Seventy five subjects, with diagnoses of ALL, AML, Burkitt's lymphoma, neuroblastoma, or Wilm's tumor, 2 or more years into survivorship, and meeting the other stated criteria, were admitted to the study. Body mass index (BMI) was calculated for each subject using the most recent height and weight, and prevalence of overweight or obesity was established using the current CDC growth charts and guidelines. Of the 75 subjects in the study, 30 (40%) were found to be overweight or obese overall, with relatively equal distribution in those categories (16 overweight vs. 14 obese). When separating subjects into their respective diagnosis categories, the rate of overweight and obesity was higher than the overall number in all groups except the neuroblastoma group (ALL 42%, AML 57%, Burkitt's 50%, Wilm's 56% vs. Neuroblastoma 21%). Subject data was analyzed for development of nutritionally related diseases since diagnosis of cancer. Forty nine (65%) were found to have developed these types of diseases including overweight/obesity, osteoporosis, restrictive airway disease, hypothyroidism, hypertension, gallbladder disease, hypercholesterolemia, and anemia. When overweight and obesity were excluded, 20 subjects (27%) remained. Forty seven (63%) of the 75 total subjects in the study had some type of nutrition education, 45 (60%) received nutrition intervention, and 25 (33%) received nutrition support. I (open full item for complete abstract)

PHD, Kent State University, 2025, College of Public Health

As cancer incidence and mortality continue to rise in the US, concerns about inequitable access and utilization of cancer care services across the cancer care continuum have grown. Cancer screening compliance and timely cancer treatment initiation are critical factors in improving outcomes and reducing disparities. Despite advancements cancer research and prevention efforts, many patients are still being diagnosed with late-stage cancers and experiencing delays in cancer treatment initiation. This dissertation aims to explore these inequities by evaluating the impact of Cleveland Clinic Taussig Cancer Center's patient navigation program on breast and colorectal cancer screening rates as well as identifying patient characteristics associated with screening noncompliance and treatment delays. These findings will provide insights to help Taussig Cancer Center administrators and clinicians design targeted interventions to better support high-risk patient populations.

PHD, Kent State University, 2024, College of Arts and Sciences / Department of Biological Sciences

Dendritic cell (DC)-based anti-cancer vaccines have been ineffectual as a monotherapy for invasive cancer. We therefore formulated a combined therapy approach that exploits the impeccable T cell-sensitizing capacity of dendritic cells and either of two small molecule inhibitor drugs, with the expectation of improved anti-cancer activity. The first, Lapatinib, is a potent inhibitor of epidermal growth factor receptor-family kinases. In conjunction with in vitro vaccine surrogates interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α), Lapatinib synergistically enhanced metabolic suppression for a panel of murine breast carcinoma lines. In addition, this combination increased cell death significantly over single treatments, with the presence of several cellular markers (Annexin V, Propidium iodide staining and executioner caspase activation) consistent with an apoptotic mechanism. Additionally, in an orthotopic model of HER-2 breast cancer, combination therapy resulted in significant tumor regression compared to single treatments, including a trend towards extended survival. Assessment of specific tumor infiltrating lymphocyte (TIL) subpopulations within tumors showed insignificant infiltrates into tumors from either untreated or Lapatinib-only treated mice, substantial and expected increases in various lymphocyte populations at both tumor margins and infiltrating into the tumor in mice that received DC-based vaccination alone and also in mice receiving both DC vaccination and Lapatinib. This finding implicates that Lapatinib is not immunomodulatory by itself but suggests that it may sensitizes tumor cells to the lymphocyte-produced cytokines already being secreted at the site of disease. The second tested drug was the novel imipridone, TIC10/ONC201. It was evaluated in conjunction with Th1 cytokines in a panel of phenotypically diverse human breast and human lung cancer cell lines. When combined with the Th1 cytokine effectors, TNF-α and IFN-γ, TIC10/ONC201 (open full item for complete abstract)

PHD, Kent State University, 2024, College of Public Health

This study focused on evaluating the patient-reported psychological outcomes (PRPOs), including anxiety, depression, cancer-related post-traumatic stress disorder symptoms (CR-PTSD), fear of cancer recurrence (FCR), and post-traumatic growth (PTG), among surgically treated colorectal cancer (CRC) patients. Additionally, this study examined the association between coping strategies and these PRPOs. The research involved 23 CRC patients undergoing curative surgery. With the exception of FCR, which was measured only post-surgery, the study conducted assessments of all PRPOs and coping strategies at two crucial points: before and after the surgical intervention. Results demonstrated a significant reduction in anxiety levels post-surgery, while depression scores remained unchanged. PTG, particularly in the dimensions of Relating to Others and Appreciation of Life, showed significant increases, indicating potential positive psychological adaptation following surgery. In contrast, CR-PTSD symptoms were minor and exhibited negligible changes that were not statistically significant. For coping strategies, there was a significant improvement in problem-focused coping post-surgery, whereas emotion-focused and avoidant coping strategies remained unchanged. Despite improvements in certain psychological outcomes and coping strategies, the study identified a high frequency of FCR among participants post-surgery, with 70% reporting elevated levels (≥12). Regression analysis showed that problem-focused coping strategies were significantly associated with reduced anxiety levels and positively correlated with PTG factors over time. These findings highlight the importance of adaptive coping mechanisms in affecting psychological outcomes after CRC surgery. The persistent high levels of FCR post-surgery underline the need for targeted psychosocial interventions to address this prevalent concern among CRC survivors. In conclusion, this research underscores the complexity of psychological (open full item for complete abstract)

Bachelor of Sciences, Ohio University, 2023, Biological Sciences

Globally, metastasis causes approximately 90% of mortality in cancer, making it a leading cause of death. In the United States, in both men and women, lung cancer is the second most prevalent cancer, with over 283,000 new cases estimated to be diagnosed in 2023. Both the tumor microenvironment (TME) and macropinocytosis have been shown to play a role in invasion, proliferation, and recurrence of cancers. Dr. Xiaozhuo Chen's lab at Ohio University studied the effects of the TME on cancer cells by performing RNA sequencing on A549. A549 are non-small cell human lung cancer (NSCLC) cells, which showed a consistent, significant upregulation of Stanniocalcin 1(STC1) gene expression when treated with extracellular ATP (eATP) and TGF-β. STC1 is a protein hormone involved in the regulation of the calcium phosphate balance, as well as ATP synthesis in mitochondria within the cell. Further studies showed that knock down of the STC1 gene led to reduced invasion and proliferation when compared to the untreated A549 cells. The aim of this project was to perform two main studies; one, to identify and assess macropinocytosis in a variety of cancer cell lines, and two, to investigate the effects of the STC1 gene on macropinocytosis. Using ATP concentration assays and IPA3 inhibition assays, macropinocytosis was examined in 11 cancer cell lines of varying cancer types. Macropinocytosis was confirmed with fluorescence microscopy by the colocalization of green fluorescent ATP and red fluorescent dextran. The impact of the knock-out of STC1 on macropinocytosis in A549 cells was investigated and quantified using ImageJ. The fluorescence microscopy study revealed that STC1 gene did play a role in macropinocytosis as predicted, which may be important for its effect on proliferation and invasion, the first step of metastasis.

Doctor of Philosophy, The Ohio State University, 2020, Communication

Introduction: Surrogate information seeking (SIA), or the act of seeking information on behalf of another, is a common health behavior. However, the phenomena remains under studied. The first study tests key propositions of the Lay Information Mediary Behavior (LIMB) model in order to understand surrogates' motivations for SIA, engagement in active and passive SIA behaviors, and willingness to share information with care recipients. The second study tests an extended Cognitive Mediation Model (CMM) to further understand the cognitive mechanisms linking surrogates' seeking and sharing behaviors. Study 1: Semi-structured interviews were conducted with caregivers of breast, endometrial, and ovarian cancer patients (n = 19). Thematic analysis of these interviews suggested that caregivers engaged in active and passive SIA for intrinsic and extrinsic reasons. Caregivers predominantly sought information to close their own knowledge gaps, but they still shared new or novel information with their care recipient. Study 2: A cross-sectional survey was administered to the caregivers of breast cancer patients diagnosed within the last two years (n = 130). Partial support was found for the proposed model. Distal variables including surveillance gratifications, information requests, and caregivers' perception of patient information gathering capacity were associated with active and passive SIA behaviors. SIA behaviors, in turn, were associated with attention and elaboration. Perceived knowledge and elaboration were associated with sharing information with care recipients, but cognitive processing did not play a role in caregivers' perceptions of knowledge. Conclusion: Taken together, the studies in this dissertation suggest that while information surrogates are occasionally extrinsically motivated, most SIA is intrinsically-motivated. Caregivers engage in active and passive SIA, and share with their care recipients. Additional motivations, such as surveillance gratifications and p (open full item for complete abstract)

Doctor of Philosophy, The Ohio State University, 2011, Psychology

Advanced and recurrent breast cancer patients experience negative biobehavioral sequelae following diagnosis. Poor marital quality has also been shown to worsen biobehavioral trajectories in earlier-stage cancer patients (e.g., Yang & Schuler, 2009; Schuler et al., under review). However, the contribution of poor marital quality among advanced or recurrent cancer patients coping with a health crisis remains unclear. This study tested the longitudinal covariation between poor marital quality and psychological distress, individual differences, health behaviors, endocrine and immune functioning, and physical health in advanced and recurrent breast cancer patients (N=98). Mixed-effects modeling compared trajectories for women in distressed marriages (n=23) to those in non-distressed marriages (n=75) at diagnosis and across a 12-month follow-up. Compared with patients in a non-distressed marriage, those in a distressed marriage showed significantly greater baseline total mood disturbance (p<.001) and differential rate of mood disturbance change across follow-up (p=.018). Immune differences were also present, with the Distressed group showing significantly higher Con A at baseline relative to the Non-Distressed group (p=.052), which persisted across 12-month follow-up. Clinical relevance and recommendations are described.

Doctor of Philosophy, The Ohio State University, 2006, Pharmacy

Previous studies in our laboratory showed that low-dose suramin, an inhibitor of fibroblast growth factor action, enhances sensitivity of various human tumors in preclinical and clinical studies to chemotherapy. Chemosensitization required apoptosis, and increased the extent and duration of the induction of apoptosis. The primary focus of this dissertation research was to explore, in preclinical studies, therapeutic approaches for therapy enhancement based on this mechanism. A phase III clinical trial in superficial bladder cancer, which emanated from our laboratory, showed that optimizing mitomycin C delivery nearly doubled the recurrence-free survival of treated patients to 40%. Tumor sensitization with suramin might yield further therapeutic improvements, and was investigated in in vitro and in vivo studies. Studies in Chapter 2 demonstrated enhanced antitumor activity of mitomycin C, administered at subtherapeutic and therapeutic regimens. Various preclinical and clinical studies determined that suramin sensitized tumor tissue at low but not at high concentrations, presumably due to additional pharmacologic effects at elevated concentrations. Studies to overcome this limitation, especially in tumors containing high fibroblast growth factor concentrations, used pentosan polysulfate, another nonspecific FGF inhibitor. This agent was also a chemosensitizer, but combined use with suramin did not increase the overall efficacy (Chapter 3). Radiotherapy depends on induction of apoptosis for its anticancer effect, as is the case for many forms of chemotherapy, and led to our evaluation of suramin as radiosensitizer. Results in Chapter 4 and Chapter 5 showed that low-dose suramin sensitized the radiation response of both radiosensitive (prostate PC-3) and relatively radioresistant (pharynx FaDu, pancreatic Hs 766T) xenograft tumors, thereby further extending the clinical application of suramin to modulate radiotherapy. More importantly, the radiosensitizaiton effect of s (open full item for complete abstract)

Master of Science, Miami University, 2011, Family and Child Studies

This study examined compliance in mammography screening among a sample of African American and Caucasian women aged 40 and over, using data from the 2005 Health Information National Trends Survey (HINTS). The socio-ecological model helped to identify the psychosocial associations that influence breast cancer screening. Compared to Caucasian women, African American women reported significantly higher psychological distress (M=1.7, SD=.69; M=1.9, SD=.84, respectively). Logistic regression indicated that race (z = 5.556), age (z = 22.933), household income (z = 8.398), health coverage (z = 6.772), and having a family history of breast cancer (z = 5.167) have significant predictive contributions to compliance.

Doctor of Philosophy, Case Western Reserve University, 2025, Pathology

Despite an explosion in our knowledge of cancer and the development of novel therapies over the past two centuries, this group of diseases still claim the lives of millions each year. The work presented herein approaches cancer from two perspectives: firstly, to improve therapeutic options via exploiting chromosomal instability, and secondly to explore factors contributing to cancer disparities. The first part of the thesis focuses on breast cancer. This is a highly heterogenous disease, partially due to the tendency of breast cancer cells to accumulate genomic instability. An unstable genome promotes adaptation and cell survival, but can also be therapeutically exploited, as inducing excessive levels triggers cancer cell death. The work described here outlines several methods to accomplish this. First, we demonstrate that CDK7-blockade causes cells to lose their ability to organize DNA, leading to mitotic catastrophe. In a second study, we find that targeting the mitotic kinase NEK2 potentiates response to CDK4/6 inhibition by driving maladaptive levels of instability and cell death. The second component of this thesis evaluates the intersection of race and environment on cancer disparities. To diminish the deeply ingrained disparities that exist in cancer, we must understand the complex interplay of factors underlying them, and be willing to make changes to address them. Our studies reveal that, in Ohio, communities with the greatest racial and ethnic diversity are more likely to be exposed to environmental contaminants. Those communities with both highly minoritized individuals and the greatest environmental burden suffered the greatest rates of cancer, particularly lung/bronchus cancer. These findings underscore the importance of focusing environmental remediation and disease prevention efforts on minoritized communities suffering the greatest health burden. Together, we discovered two levels for preventing poor cancer outcomes. We identified cellula (open full item for complete abstract)

Doctor of Philosophy, Case Western Reserve University, 2025, Biomedical Engineering

Due to recent advancements in the field of cancer imaging and diagnostic techniques, most solid human cancers are diagnosed at earlier stages while the cancer is still localized to a primary tumor site. For this reason, surgery remains the cornerstone of curative treatment with the primary objective of surgical intervention being the complete removal of the tumor, aiming to eliminate cancerous tissues. Ideally, this goal is achieved in a single surgical procedure, ensuring no residual malignant tissue remains. However, achieving complete resection can be challenging, particularly in traditional surgeries where surgeons primarily rely on gross visual inspection and tactile feedback to identify and remove the tumor. This increases the risk of leaving behind microscopic cancer cells that are not visible or palpable during the procedure. As a result, there is a significant risk of Positive Surgical Margins (PSMs), where cancer cells are present at the edge of the resected tissue. PSMs are a critical concern because they often result in tumor recurrence and necessitate additional treatments including adjuvant therapies, such as radiation therapy, chemotherapy and so on. These therapies, while essential for reducing the risk of recurrence, substantially increase the overall cost and complexity of treatment and add to the physical and emotional burden on patients, prolonging the recovery process and potentially impacting their quality of life. The challenge of achieving complete tumor resection underscores the need for improved surgical technologies and adjunct treatments that can enhance the live visualization of tumor removal and simultaneously treat the remaining tissues to reduce tumor recurrence and improve overall survival. To address these challenges, this research aims to enhance treatment strategies for prostate cancer (PCa) through innovative theranostic approaches utilizing Prostate-Specific Membrane Antigen (PSMA) as a key biomarker. PSMA is notably overex (open full item for complete abstract)

Doctor of Philosophy, The Ohio State University, 2023, Biomedical Engineering

Cancer metastasis is a complex, systemic, and non-random process requiring tumor cells to both adapt to and manipulate a multitude of microenvironments. Given this complexity, traditional 2D cell culture models offer insufficient structural and biological relevance, while animal models face obstacles in real-time analysis, experimental control, and translational success. As an alternative to address these barriers, this dissertation discusses development of tissue engineered microfluidic device-based tumor-on-a-chip platforms to isolate phases of metastatic colonization and study premetastatic microenvironmental changes. In this dissertation, this hydrogel-based technology was applied in three different aspects of metastatic progression. First, a thyroid metastasis-on-a-chip model was developed to study metastasis suppressor gene RCAN1-4 and its impact on downstream lung colonization. Second, 3D hydrogel scaffolds were implemented to investigate colorectal cancer-induced collagen remodeling by stromal fibroblasts and pericytes during premetastatic niche development. Third, observations of cancer-induced collagen remodeling were used to inform design of a liver premetastatic niche-on-a-chip model to further interrogate immune-myofibroblast crosstalk in response to colorectal cancer signaling and establish the relationship between this crosstalk and metastatic colonization.

Master of Science, The Ohio State University, 2023, Public Health

Background: In the United States, individuals assigned female at birth have about a 13% lifetime risk of breast/chest cancer. Those with a family history of breast/chest cancer or a BRCA gene mutation are at elevated risk of the disease, with greater than or equal to 20% lifetime risk. However, only a small proportion of individuals at high risk utilize available preventive services like mammography screening. Individuals of sexual minority identity and Black individuals experience increased levels of healthcare distrust. Healthcare distrust in turn is associated with lower rates of mammography screening utilization. Aim: Our study aim was to examine the relationship between healthcare distrust, sexual minority identity, and Black race to determine how they are related to mammography screening concordance rates among individuals at objectively elevated risk. We further sought to determine if healthcare distrust mediated the relationship between sexual minority identity and mammography discordance. Methods: We used survey data from The Daughter Sister Mother Project, a cross-sectional web survey conducted from 2018 to 2019 that used convenience sampling methods. Eligible participants were 18 to 75 years of age, identified as non-Hispanic White or non-Hispanic Black/African American, identified their sex as “female”, had a family history of breast/chest cancer or a BRCA gene mutation, and had no prior history of cancer. Our analysis focused on the high-risk subsample of participants, defined as individuals with a self-reported BRCA mutation or greater than 20% lifetime risk according to 1 or more risk prediction models. The primary exposure for this analysis was sexual minority identity and the primary outcome was mammography concordance, defined as reporting receipt of a mammogram within the last year if recommended according to National Comprehensive Cancer Network (NCCN) screening guidelines for women at high risk. Healthcare distrust was measured using the Rev (open full item for complete abstract)

Doctor of Philosophy, The Ohio State University, 2022, Biomedical Sciences

Small cell lung cancer (SCLC) is an extremely aggressive neuroendocrine tumor, accounting for approximated 13% of all lung cancer cases. SCLC is characterized by rapid growth and early metastasis. Despite marked improvements in the number and efficacy of targeted, therapeutic options and overall survival rates in SCLC have remained nearly unchanged for almost three decades. The lack of significant progress can be attributed to our poor understanding of the biology of SCLC. Although immune checkpoint inhibitors were recently approved as front-line therapies for SCLC, we still need to better understand the mechanisms responsible for the selective vulnerability of some SCLCs to these inhibitors. Recent work utilizing sequencing data and single cell analyses identified four distinct subsets of SCLC, based on the expression levels of the transcription factors ASCL1, NEUROD1, POU2F3 and YAP1. Each subset was found to have its own distinct biology and therapeutic vulnerabilities. However, these subsets appear to be phenotypically unstable, representing snapshots in the gradual evolution of a tumor that exhibits significant plasticity. Tumor evolution, a product of this plasticity, results in the emergence of significant intratumoral heterogeneity which plays an important role in multiple aspects of SCLC development and progression, including cell survival and proliferation, metastasis and angiogenesis. The recent paradigm shifting discoveries in the biology of SCLC are now beginning to inform the design of new therapeutic strategies for the management of this intractable disease. Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1) is an oncofetal protein that is emerging as a therapeutic target and is co-expressed with BCL2 in multiple tumor types due to microRNA coregulation. We hypothesize that ROR1-targeted therapy is effective in small cell lung cancer and synergizes with therapeutic BCL2 inhibition. Tissue microarrays (TMAs) and formalin-fixed paraffin-embedded (F (open full item for complete abstract)

Doctor of Philosophy in Biomedical Sciences (Ph.D.), University of Toledo, 2021, Biomedical Sciences (Cancer Biology)

Cancer remains a significant public health burden worldwide, and advances in treatment are aimed at delivering a deathblow to cancer cells, while sparing normal cells. Hence, the ongoing search for novel targets has led to the discovery of a cytoplasmic cis ATR (Ataxia Telangiectasia and Rad3 Related) protein whose function is normal in cells at homeostasis, but when predominant in the cytoplasm, it provides an oncogenic drive through evasion of apoptosis. ATR is a member of the PIKK (Phosphatidylinositol 3-kinase-related kinase) family of protein kinases and nuclear ATR plays a crucial role in DNA damage responses (DDR) by phosphorylating hundreds of downstream proteins. However, ATR is also present in the cytoplasm as either a cis or trans isomeric form, depending on Pin1 which converts cis ATR to trans ATR. Following DNA damage, Pin1's isomerization of cytoplasmic ATR is inhibited leading to an increase in cytoplasmic cis ATR levels. This DNA damage can be from an acute insult or from effects of accumulated damage from the aging process. Following DNA damage, cytoplasmic cis ATR, via its BH3 domain, binds to t-Bid at the outer mitochondrial membrane and sequesters t-Bid to prevent t-Bid binding of pro-apoptotic Bax/Bak protein thus, suppressing apoptosis. Therefore, the levels of cis ATR in the cytoplasm could determine cell fate: death or immortality. With a predominance of cis ATR in cell cytoplasm, there is an inability of the cells to be killed by apoptosis, leading to DNA damage accumulation, genomic instability, and thus oncogenesis. This phosphorylation-dependent peptidyl-prolyl isomerization of ATR by Pin1 serves as a regulatory tool that can be taken advantage of since PP2A can dephosphorylate the key phosphorylated residue in ATR that Pin1 recognizes. With PP2A regulation of ATR, it is possible to shift the balance between the cis and trans forms of cytoplasmic ATR. This is particularly important because it provides a potential strategy in enhancing can (open full item for complete abstract)

Doctor of Philosophy, Case Western Reserve University, 2021, Nursing

Being a distance caregiver (DCG) for a patient with cancer creates unique and challenging stressors that put them at risk for adverse psychological outcomes. A DCG is an informal care provider who lives one or more hours of travel time away from the patient. This study examined the relationships between DCG stressors, psychological detachment, and anxiety, and explored the possible mediating effect of psychological detachment on the relationship between DCG stressors and anxiety. DCG tasks can be described as work and psychological detachment, a concept studied among workers, has been shown to ameliorate the negative effect of stressors. Among DCGs, psychological detachment was defined as refraining from caregiving thoughts and tasks. Given that DCGs and workers experience similar stressors and outcomes, studying psychological detachment in DCGs provides information to better understand their unique experience. The Stressor-Detachment model provided a framework for understanding the role of psychological detachment in the relationship between DCG stressors and anxiety. This study was a cross sectional, descriptive research design and a secondary analysis of data collected for a RCT study Closer: A Videoconference Intervention for Distance Caregivers. Adult DCGs of cancer patients (n=86) completed the Recovery Experience Questionnaire psychological detachment subscale (adapted for DCGs) and the PROMIS® anxiety short form. Patient data were included as proxy measures for the variable 'stressors of being a DCG'. The results of this research study were: 1) DCGs reported low psychological detachment scores which indicated they had difficulty refraining from thoughts and tasks of caregiving, 2) a positive association was found between patient depression (a DCG stressor) and DCG anxiety, r (67) = .324, p = .007, 95% CI [.150, .484], and 3) DCG psychological detachment did not serve as a mediator between DCG stressors and anxiety symptoms. This study contributes (open full item for complete abstract)

Master of Science (MS), University of Toledo, 2020, Pharmaceutical Sciences (Pharmacology/Toxicology)

The zebrafish, Danio rerio, was used to develop a colon cancer model in order to show the therapeutic effects of various chemotherapeutic drugs. Microinjections were used to inject the three-day post fertilization, 3dpf, zebrafish with colon cancer cells, HCT116. The success of this experiment was tracked by using fluorescent GFP tagged wild type cancer cells and taking photos of the translucent zebrafish with fluorescent imaging. Recently, we identified three thienopyridine analogs namely TPH104, TPH104c and TPH104m that have shown beneficial activity against colon cancer cells HCT116 in in vitro settings. These promising lead compounds were set to test their safety in vivo setting in zebrafish larvae five-day post fertilization, 5dpf. An acridine orange staining test was done to analyze the zebrafish embryos after being exposed to the various chemotherapeutic drug concentrations. The results of the toxicity assays allowed us to determine a therapeutic dosage for the zebrafish larvae and identified changes in morphology, heart rate and behavior. Please note that due to COVID-19 crisis this work was disrupted and was not able to be replicated to draw a meaningful statistical significance, hence the work presented here should be considered preliminary findings only.

Master of Science, The Ohio State University, 2020, Public Health

Breast cancer is the most common form of cancer among women. Triple negative breast cancers are a particularly aggressive subtype of breast cancer, accounting for an outsized proportion of disease related deaths. Metastatic TNBC is not curable and has limited options for palliative treatments, relying on a series of carefully managed monotherapies to slow disease progression. Advances in monitoring techniques may aid in the management of therapies in the metastatic context, as well as provide additional, actionable information on emergent biomarkers and targetable sites. In this work, we detail the application of PyClone, a hierarchical-Bayes framework for modeling clonal cell populations in cancer, to deep targeted panel sequencing of circulating tumor DNA, derived from serum collected in the phase-II biomarker study of cabozantinib in mTNBC. We demonstrate that important lesions can be tracked simultaneously through as many as eight time points in treatment, and that these lesions can be modeled into representative clonal populations, despite data sparsity. Our findings indicate that individuals can display markedly different clonal dynamics over similar windows of time, with identical diagnoses and treatments. Modeling variant populations gives us limited but valuable insight into phylogenetic origins of tumor clone populations. We also observe discordance between prognostic tumor fraction estimates of ctDNA and RECIST response categories, as well as demonstrate the ability to use whole exome sequencing of ctDNA to make computational predictions on the emergence of novel neoantigens throughout the course of treatment. Our successful application of these technologies suggests that ctDNA-based genomic profiling is an under-utilized tool for the study of cancer evolution, response to therapy, and disease progression monitoring. We suspect that ctDNA-based genomic profiling may provide valuable information through minimally invasive means in translational cancer rese (open full item for complete abstract)

Doctor of Philosophy, Case Western Reserve University, 2020, Biomedical Engineering

As the arsenal of therapeutic strategies in the fight against cancer grows, so too does the need for predictive biomarkers that can precisely guide their use in order to match patients with their optimal personalized treatment plan. Currently, clinicians often have little recourse but to initiate treatment and monitor a tumor for signs of response or progression, which exposes non-responsive patients to overtreatment, harmful side effects, and windows of ineffective therapy that increase a patient's risk of progression or metastasis. Thus, there is an urgent need for new sources of predictive biomarkers to help more effectively plan personalized treatment strategies. Radiological images acquired before treatment may contain previously untapped predictive information that can be quantified in the form of computational imaging biomarkers. The vast majority of existing computational imaging biomarkers provides analysis limited to the tumor region itself. However, the tumor environment contains critical biological information pertinent to tumor progression and treatment outcome, such as tumor-associated vascularization and immune response. This dissertation focuses on the development of new, biologically-inspired computational imaging biomarkers targeting the tumor environment for the prediction of response to a wide range of chemotherapeutic and targeted treatment strategies in oncology. First, we explore measurements of textural heterogeneity within the tumor and surrounding peritumoral environment, and demonstrate the ability to predict therapeutic response and tumor biology to neoadjuvant chemotherapy in primary and targeted therapy in primary and metastatic breast cancer. Second, we introduce morphologic techniques for the quantification of the twistedness and organization of the tumor-associated vasculature, and demonstrate their association with response and survival following four different therapeutic strategies in breast cancer MRI and non-small cell lung canc (open full item for complete abstract)